Duration Of Arrhythmia Research Articles

Transoesophageal echocardiography-guided cardioversion and thromboembolism

Abstract Background To perform electrical cardioversion of atrial fibrillation or atrial flutter with a duration of more than 48 hours, it is recommended to initiate anticoagulation therapy for at least three weeks beforehand. In cases where cardioversion is necessary earlier, it is suggested to precede the procedure with a transoesophageal echocardiography to rule out the presence of a thrombus in the left atrium (referred to as TOE-guided cardioversion). This strategy is outlined in current ESC guidelines for atrial fibrillation. However due to limited evidence, no specific level of recommendation for its use is provided. Purpose This study aimed to characterize patients treated by TOE-guided cardioversion in two hospitals and to conduct a safety analysis of the procedure. The 30-day incidence of thromboembolic events was chosen as the main safety objective, the 30-day mortality as the secondary. Method This was a retrospective, two center, cohort register study where information was obtained from patients medical records. All patients who underwent TOE-guided cardioversion between 2012-2020 in the first institute, and between 2015-2020 in the second were included. From the medical records all the patient characteristics and the clinical outcomes were identified. Result A total of 259 patients, with TOE-guided cardioversions, arrhythmia duration over 48 hours and without adequate anticoagulation therapy were included. Patient characteristics are shown in table 1. It was equal incidence of a 30-day thromboembolic event (n=6) and the 30-day mortality (n=6), 2,3% respectively. Three of the six patients died of non-cardiovascular cause. One of the 30-day thromboembolic event resulted in mortality at day 31. Table 2 summarize the data related to the thromboembolic events. There was no statistically significant predictor of any of the two endpoints when comparing the patients with event and patients without. Conclusion This study shows that the risk of thromboembolic events after TOE-guided cardioversion is not negligible, 2,3% within a 30-day follow up. The 30-day mortality was 2,3%, half of which were non-cardiovascular. To analyse potential clinical predictors for any events, larger studies specifically powered for such a question is needed.

A dynamic online nomogram predicting post-traumatic arrhythmias: A retrospective cohort study

BackgroundA nomogram is a visualized clinical prediction models, which offer a scientific basis for clinical decision-making. There is a lack of reports on its use in predicting the risk of arrhythmias in trauma patients. This study aims to develop and validate a straightforward nomogram for predicting the risk of arrhythmias in trauma patients. MethodsWe retrospectively collected clinical data from 1119 acute trauma patients who were admitted to the Advanced Trauma Center of the Affiliated Hospital of Zunyi Medical University between January 2016 and May 2022. Data recorded included intra-hospital arrhythmia, ICU stay, and total hospitalization duration. Patients were classified into arrhythmia and non-arrhythmia groups. Data was summarized according to the occurrence and prognosis of post-traumatic arrhythmias, and randomly allocated into a training and validation sets at a ratio of 7:3. The nomogram was developed according to independent risk factors identified in the training set. Finally, the predictive performance of the nomogram model was validated. ResultsArrhythmias were observed in 326 (29.1%) of the 1119 patients. Compared to the non-arrhythmia group, patients with arrhythmias had longer ICU and hospital stays and higher in-hospital mortality rates. Significant factors associated with post-traumatic arrhythmias included cardiovascular disease, catecholamine use, glasgow coma scale (GCS) score, abdominal abbreviated injury scale (AIS) score, injury severity score (ISS), blood glucose (GLU) levels, and international normalized ratio (INR). The area under the receiver operating characteristic curve (AUC) values for both the training and validation sets exceeded 0.7, indicating strong discriminatory power. The calibration curve showed good alignment between the predicted and actual probabilities of arrhythmias. Decision curve analysis (DCA) indicated a high net benefit for the model in predicting arrhythmias. The Hosmer-Lemeshow goodness-of-fit test confirmed the model's good fit. ConclusionThe nomogram developed in this study is a valuable tool for accurately predicting the risk of post-traumatic arrhythmias, offering a novel approach for physicians to tailor risk assessments to individual patients.

Chamber-specific contractile responses of atrial and ventricular hiPSC-cardiomyocytes to GPCR and ion channel targeting compounds: A microphysiological system for cardiac drug development

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) have found utility for conducting in vitro drug screening and disease modelling to gain crucial insights into pharmacology or disease phenotype. However, diseases such as atrial fibrillation, affecting >33 M people worldwide, demonstrate the need for cardiac subtype-specific cells. Here, we sought to investigate the base characteristics and pharmacological differences between commercially available chamber-specific atrial or ventricular hiPSC-CMs seeded onto ultra-thin, flexible PDMS membranes to simultaneously measure contractility in a 96 multi-well format. We investigated the effects of GPCR agonists (acetylcholine and carbachol), a Ca2+ channel agonist (S-Bay K8644), an HCN channel antagonist (ivabradine) and K+ channel antagonists (4-AP and vernakalant). We observed differential effects between atrial and ventricular hiPSC-CMs on contractile properties including beat rate, beat duration, contractile force and evidence of arrhythmias at a range of concentrations.As an excerpt of the compound analysis, S-Bay K8644 treatment showed an induced concentration-dependent transient increase in beat duration of atrial hiPSC-CMs, whereas ventricular cells showed a physiological increase in beat rate over time. Carbachol treatment produced marked effects on atrial cells, such as increased beat duration alongside a decrease in beat rate over time, but only minimal effects on ventricular cardiomyocytes. In the context of this chamber-specific pharmacology, we not only add to contractile characterization of hiPSC-CMs but propose a multi-well platform for medium-throughput early compound screening.Overall, these insights illustrate the key pharmacological differences between chamber-specific cardiomyocytes and their application on a multi-well contractility platform to gain insights for in vitro cardiac liability studies and disease modelling.

One-year outcome of wide-area pulmonary vein isolation using the third-generation visually guided laser balloon

Abstract Background The third-generation laser balloon (LB3) is equipped with an ultra-compliant balloon and a motor-driven laser generator, which contribute to durable and gapless isolated lesion creation. However, the efficacy of wide-area pulmonary vein (PV) isolation (PVI) using LB3 remains to be elucidated. Purpose This study aims to investigate efficacy of wide-area PVI using LB3. Methods This is a single-center retrospective study. Patients with atrial fibrillation (AF) who underwent LB3 ablation during the period from August 2021 to June 2022 were enrolled. All PVs were electrically isolated only by LB3. After initial circular ablation, LB3 was inflated to a larger size at each PV, and the isolation area was extended. After ablation, voltage maps of the left atrium were obtained by high-resolution mapping catheters to evaluate isolation areas (<0.1mV). Follow-up included a 12-lead electrocardiogram, Holter monitoring, and/or pacemaker/implantable cardioverter-defibrillator interrogation. The efficacy endpoint was defined as freedom from atrial tachyarrhythmia (ATa) between months 3 and 12. Results Forty-four patients with paroxysmal AF and 34 with persistent AF (mean arrhythmia duration 12.4 months, range 1–60 months) were included. First pass isolation was achieved in 90.6% (280/309) of PVs. The total laser application time was 24.1±6.4 minutes, and the total delivered energy was 15.3±3.2 kJ. The isolation area at the left- and right-sided PV antrum were 14.2±1.8 and 19.5±1.1 cm², respectively. At the end of the 12 months of follow-up, the freedom from ATa was 78.2% in patients with paroxysmal AF and 78.0% in persistent AF, which indicates ATa free survival at one year was similar in both groups (P=0.91). Conclusions Wide-area PVI using LB3 may lead to favorable outcomes in patients with AF.Fluoroscopic and endoscopic imageKaplan-Meier curves and voltage map

Protection by L-arginine against Epinephrine-induced Arrhythmia and Cardiotoxicity

Nitric oxide is important in control of coronary blood flow, cardiomyocyte contractility, cardiac rhythm, and thrombogenicity. We aimed to investigate the effect of the nitric oxide precursor L-arginine on cardiac arrhythmia and myocardial injury induced by epinephrine in male Sprague-Dawley rats. The possible modulation of L-arginine effects by methylene blue (MethyB), a nitric oxide synthase inhibitor was also examined. Cardiac arrhythmia was induced with 10μg/kg epinephrine given intravenously (i.v.). L-arginine (200mg/kg) or L-arginine and MethyB (100mg/kg) were intraperitoneally (i.p.) administered prior to i.v. epinephrine. Other groups received i.p. saline, only L-arginine or only MethyB (100mg/kg). Results showed that compared with the saline control, epinephrine caused a significant bradycardia (188.7±24.4 vs. 405.6±1.19beats/min), increased QRS duration (0.039±0.006 vs. 0.0185±0.0001s), decreased R wave amplitude (0.18±0.01 vs. 0.23±0.011mv), and ventricular extrasystoles. L-arginine alone showed no significant effect on heart rate (380.8±10.0 vs. 405.6±1.19beats/min) but increased QRS duration (0.029±0.0002 vs. 0.0185±0.0001s), and R wave amplitude (0.47±0.01 vs. 0.23±0.011mv). L-arginine given prior to epinephrine prevented bradycardia, shortened the duration of arrhythmia and decreased the number of extrasystoles. The administration of L-arginine and MethyB almost completely suppressed epinephrine-induced ventricular arrhythmias. Epinephrine caused severe degeneration of muscle fibres, widening of intercellular spaces, cellular infiltrations and interstitial haemorrhage. L-arginine markedly attenuated, while L-arginine/MethyB completely prevented these changes. It is concluded that L-arginine protects against cardiac arrhythmias and cardiac tissue damage caused by epinephrine.

Moderate Endurance Exercise Increases Arrhythmia Susceptibility and Modulates Cardiac Structure and Function in a Sexually Dimorphic Manner.

Although moderate endurance exercise has been reported to improve cardiovascular health, its effects on cardiac structure and function are not fully characterized, especially with respect to sexual dimorphism. We aimed to assess the effects of moderate endurance exercise on cardiac physiology in male versus female mice. C57BL/6J mice of both sexes were run on a treadmill for 6 weeks. ECG and echocardiography were performed every 2 weeks. After 6 weeks of exercise, mice were euthanized, and triple parametric optical mapping was performed on Langendorff perfused hearts to assess cardiac electrophysiology. Arrhythmia inducibility was tested by programmed electrical stimulation. Left ventricular tissue was fixed, and RNA sequencing was performed to determine exercise-induced transcriptional changes. Exercise-induced left ventricular dilatation was observed in female mice alone, as evidenced by increased left ventricular diameter and reduced left ventricular wall thickness. Increased cardiac output was also observed in female exercised mice but not males. Optical mapping revealed further sexual dimorphism in exercise-induced modulation of cardiac electrophysiology. In female mice, exercise prolonged action potential duration and reduced voltage-calcium influx delay. In male mice, exercise reduced the calcium decay constant, suggesting faster calcium reuptake. Exercise increased arrhythmia inducibility in both male and female mice; however, arrhythmia duration was increased only in females. Lastly, exercise-induced transcriptional changes were sex dependent: females and males exhibited the most significant changes in contractile versus metabolism-related genes, respectively. Our data suggest that moderate endurance exercise can significantly alter multiple aspects of cardiac physiology in a sex-dependent manner. Although some of these effects are beneficial, like improved cardiac mechanical function, others are potentially proarrhythmic.

Atrial fibrillation: real-life experience of a rhythm control with electrical cardioversion in a community hospital

BackgroundAtrial fibrillation is the most prevalent sustained cardiac arrhythmia. Electrical cardioversion, a well-established part of the rhythm control strategy, is probably underused in community settings. Here, we describe its use, safety, and effectiveness in a cohort of patients with atrial fibrillation treated in rural settings.MethodsIt is a retrospective cohort study. Data on all procedures from January 1, 2016, till December 1, 2022, in Tarusa Hospital, serving mostly a rural population of 15,000 people, were extracted from electronic health records. Data on the procedure’s success, age, gender, body mass index, comorbidities, previous procedures, echocardiographic parameters, type and duration of arrhythmia, anticoagulation, antiarrhythmic drugs, transesophageal echocardiography, and settings were available.ResultsAltogether, 1,272 procedures in 435 patients were performed during the study period. The overall effectiveness of the procedure was 92%. Effectiveness was similar across all prespecified subgroups. Electrical cardioversion was less effective in patients undergoing the procedure for the first time (86%, 95% CI: 82-90) compared to repeated procedures (95%, 95% CI: 93-96), OR 0.39 (95% CI: 0.26-0.59). Complications were encountered in 13 (1.02%) procedures but were not serious.ConclusionsElectrical cardioversion is an immediately effective procedure that can be safely performed in community hospitals, both in inpatient and outpatient settings. Further studies with longer follow-up are needed to investigate the rate of sinus rhythm maintenance in these patients.

Study of antiarrhythmic activity 2-(n-butylpyrrolidine)-N-(2-bromophenyl)carboxamide hydrochloride

Objective. To study the efficacy of a new derivative 2-(alkylpyrrolidine)-N-(aryl)carboxamide with high antiarrhythmic activity. Materials and methods. To study the antiarrhythmic activity of the compound, the experiment was carried out on models of arrhythmia caused by intravenous administration of aconitine and adrenaline. The effect was estimated by its ability to prevent the onset of arrhythmia, prolong the survival time of the animals or by the duration of an arrhythmia attack. In addition, the electrocardiogram of awake rats was analyzed. The studied compound and the comparison drug (lidocaine) were injected to the animals intravenously in effective antiarrhythmic doses. Results. In aconitine arrhythmia 2-(n-butylpyrrolidine)-N-(2-bromophenyl) carboxamide hydrochloride provides statistically significant limitation of the duration of arrhythmia attacks in experimental animals (1.7 times) in comparison with the control and also reduction of arrhythmia duration in comparison with lidocaine (2.5 times); besides, this compound guarantees animals’ survival in 100 % of cases. When causing arrhythmia by adrenaline administration, the compound does not prevent the occurrence of cardiac rhythm disorder. The electrocardiogram readings of animals do not change significantly. Conclusions. 2-(n-butylpyrrolidine)-N-(2-bromophenyl) carboxamide hydrochloride (compound K-23) shows visible activity in models of arrhythmia caused by administration of aconitine and calcium chloride, which may indicate its ability to impede the sodium flow through the cell membrane by slowing depolarization of cardiomyocytes. Since the compound studied, demonstrates high antiarrhythmic activity without changing the ECG readings, the drug created on its basis may be effective.

Inhibition of Cardiac Kv4.3/KChIP2 Channels by Sulfonylurea Drug Gliquidone.

The Kv4.3 channel features fast N-type inactivation and also undergoes a slow C-type inactivation. The gain-of-function mutations of Kv4.3 channels cause an inherited disease called Brugada syndrome (BrS), characterized by a shortened duration of cardiac action potential repolarization and ventricular arrhythmia. The sulfonylurea drug gliquidone, an ATP-dependent K+ channel antagonist, is widely used for the treatment of type 2 diabetes. Here, we report a novel role of gliquidone in inhibiting Kv4.3 and Kv4.3/KChIP2 channels that encode the cardiac transient outward K+ currents responsible for the initial phase of action potential repolarization. Gliquidone results in concentration-dependent inhibition of both Kv4.3 and Kv4.3/KChIP2 fast or steady-state inactivation currents with an IC50 of approximately 8 μM. Gliquidone also accelerates Kv4.3 channel inactivation and shifts the steady-state activation to a more depolarizing direction. Site-directed mutagenesis and molecular docking reveal that the residues S301 in the S4 and Y312A and L321A in the S4-S5 linker are critical for gliquidone-mediated inhibition of Kv4.3 currents, as mutating those residues to alanine significantly reduces the potency for gliquidone-mediated inhibition. Furthermore, gliquidone also inhibits a gain-of-function Kv4.3 V392I mutant identified in BrS patients in voltage- and concentration-dependent manner. Taken together, our findings demonstrate that gliquidone inhibits Kv4.3 channels by acting on the residues in the S4 and the S4-S5 linker. Therefore, gliquidone may hold repurposing potential for the therapy of Brugada syndrome. SIGNIFICANCE STATEMENT: We describe a novel role of gliquidone in inhibiting cardiac Kv4.3 currents and the channel gain-of-function mutation identified from patients with Brugada syndrome, suggesting its repurposing potential for therapy for the heart disease.

On-chip, non-invasive detection of all atrial arrhythmias for immediate and accurate characterization in adult rats

Abstract Background To monitor and record the occurrence and duration of cardiac arrhythmias in freely moving animals, ECG telemetry devices are often used. However, traditional telemetry devices require complex equipment unsuitable for on-site application in most animal housing facilities. Additionally, current atrial arrhythmias detection algorithms are mainly based on ECG R-R interval variability for atrial fibrillation (AF) detection. Such algorithms do not allow the detection of stable R-R interval atrial arrhythmias such as flutter. Thus there is currently a lack of non-invasive methods allowing automated detection of all atrial arrhythmias subtypes, thereby precluding in-depth research into general and subtype-specific mechanisms and treatment. Purpose Here we aim to create a non-invasive system allowing fast and accurate on-site detection and characterization of all atrial arrhythmias in rats. Methods Our atrial arrhythmia detector system was made of an on-skin ECG sensor, a low-power microprocessor unit, a large data storage unit and a battery. All components were assembled within a lightweight rat jacket. The filtered ECG signal was sent to the microprocessor allowing algorithm-based, real-time detection of atrial arrhythmias. The device allowed storage of ECG traces as well as arrhythmia characteristics (including type of arrhythmia and its duration). Atrial arrhythmias were induced by transesophageal atrial burst pacing in Wistar rats. These arrhythmia recordings were used to develop an AI detection method. Next, real-time detection algorithms based on R-R variability and AI were both integrated on-chip and compared using the same ECG data. Results ECG traces measured with our new system were similar to classical ECG measurements. Stored ECG traces provided the raw data for the development of an AI-based detection algorithm. The AI training was done using ECG data recorded from five different rats and reached 99.5% self-testing accuracy to detect all sub-types of atrial arrhythmias based on pre-categorized data. Using uncategorized data (n=25 from 5 rats) different from the training dataset, the AI algorithm could detect >80% of all types of atrial arrhythmias within 3s after initiation, while the rest could be detected within 10s. Though R-R interval based algorithm showed a high detection rate of 88% of AF within 10s, this method did not allow the detection of flutter or AF presenting regular R-R intervals within 1 minute after initiation. Conclusion Our atrial arrhythmia detection and analysis system provides a novel method for non-invasive investigation into atrial arrhythmias in rats and could easily be scaled for other species. It allows on-site fast and accurate detection and characterization of atrial arrhythmia subtypes without external equipment, thereby opening new possibilities for mechanistic studies and therapeutic testing, including closed-loop applications aiming for arrhythmia termination.

The Effects of Nitric Oxide Synthase Inhibition on Epinephrine-Induced Arrhythmia and Myocardial Damage

We have recently reported that methylene blue (MethyB) was able to inhibit epinephrine-induced arrhythmias and cardiac muscle injury. In this study, we investigated the effect of nitric oxide synthase inhibition by NG-nitro-L-arginine methyl ester (L-NAME) on cardiac arrhythmias, and myocardial damage induced by epinephrine in rats. Whether nitric oxide inhibition would affect the antiarrhythmic and cardiac protective actions of MethyB was also examined. L-NAME (40 mg/kg), L-arginine (200 mg/kg) + L-NAME, or MethyB (100 mg/kg) + L-NAME were given intraperitoneally (i.p.). Cardiac arrhythmia was then induced with intravenous (i.v.) injection of 10 μg/kg epinephrine. Results showed that epinephrine injection caused marked bradycardia (221.0 ± 1.37 vs. 409.4 ± 3.18 beats/min), shortened QTc interval (0.096 ± 0.0093 vs. 0.177 ± 0.0008 s), increased QRS duration (0.040 ± 0.0035 vs. 0.0185 ± 0.0002 s), decreased R wave amplitude (0.176 ± 0.0051 vs. 0.21 ± 0.0009 mv), ST segment height (-0.026 ± 0.007 vs. -0.002 ± 0.0005 mv), and induced ventricular extrasystoles. L-NAME given to untreated control rats resulted in a decrease in heart rate (288.2 ± 0.88 vs. 409.4 ± 3.18 beats/min), and increased R wave amplitude (0.436 ± 0.004 vs. 0.21 ± 0.0009 mv) compared to controls. L-NAME did not cause extrasystoles in untreated control rats but significantly increased the number of extrasystoles and duration of arrhythmia in the epinephrine-treated group. The administration of L-arginine (200 mg/kg, i.p.) to epinephrine plus L-NAME-treated rats resulted in increased heart rate and markedly decreased the number of extrasystoles and duration of arrhythmia. Methylene blue given at 100 mg/kg to rats treated with epinephrine and L-NAME caused a marked increase in heart rate. It also normalized QRS duration, prevented ST segment depression, markedly suppressed ventricular extrasystoles, and decreased the duration of arrhythmia compared with either epinephrine or L-NAME plus epinephrine-treated groups. Epinephrine injection caused disorganization, and necrosis of cardiac cells, interstitial hemorrhage, and cellular infiltrations. These changes were markedly improved by treatment with either L-NAME or L-NAME/MethyB. These results suggest that (i) inhibiting nitric oxide synthase by L-NAME increases epinephrine-induced arrhythmia which is inhibited by L-arginine or MethyB; (ii) either L-NAME alone or in combination with MethyB prevented cardiac muscle injury induced by epinephrine; (iii) L-NAME did not prevent the cardiac protective and antiarrhythmic actions of MethyB.

Correlation between Prolonged Aortic Cross Clamp and New Onset Cardiac Arrhythmia after Cardiac Surgery

Objectives: Cardiac arrhythmia involves a wide range of abnormalities associated with heart rhythm and rate disorders. It mainly refers to an irregular rhythm of the heart. It has been demonstrated through various clinical studies that aortic cross-clamp time during cardiac surgeries are independent predictors of the morbidity and mortality, and prolonged cross-clamp (XCL) time have been linked to the low cardiac output. Present study was aimed to examine the correlation between the prolonged aortic cross clamp time (XCL) in low-risk patients and the incidence of cardiac arrhythmia during cardiac surgery within 48 hours postoperatively. Methods: A retrospective study was carried out from March 2020 to February 2021 including 100 patients who underwent elective cardiac surgery as low-risk patients. The duration of XCL and new-onset cardiac arrhythmia was monitored within the first 48 hours postoperatively. Result: This study revealed a significant relationship between new onset Arrhythmia and prolonged cross clamp time (more than 90 min). It also revealed a weak correlation (r = 0.26) between the aortic cross clamp time and new onset of cardiac arrhythmia after cardiac surgery (average XCL time 60 min). Therefore, this study suggested XCL time one of important predictors of cardiac arrhythmia postoperatively. Conclusion: Prolonged aortic cross-clamp time was found to minimally affect the incidence of arrhythmia in cardiac surgery within 48-hour post-operatively in low-risk cardiac patients. Patients with cross clamp time of over 90min were observed to be the most affected by the Arrhythmia with a high prevalence rate, which further buttress on the fact that extended/prolonged XCL affect cardiac arrhythmia after cardiac surgery.

The Junctophilin-2 Mutation p.(Thr161Lys) Is Associated with Hypertrophic Cardiomyopathy Using Patient-Specific iPS Cardiomyocytes and Demonstrates Prolonged Action Potential and Increased Arrhythmogenicity.

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases; it is primarily caused by mutations in sarcomeric genes. However, HCM is also associated with mutations in non-sarcomeric proteins and a Finnish founder mutation for HCM in non-sarcomeric protein junctophilin-2 (JPH2) has been identified. This study aimed at assessing the issue of modelling the rare Finnish founder mutation in cardiomyocytes (CMs) differentiated from iPSCs; therefore, presenting the same cardiac abnormalities observed in the patients. To explore the abnormal functions in JPH2-HCM, skin fibroblasts from a Finnish patient with JPH2 p.(Thr161Lys) were reprogrammed into iPSCs and further differentiated into CMs. As a control line, an isogenic counterpart was generated using the CRISPR/Cas9 genome editing method. Finally, iPSC-CMs were evaluated for the morphological and functional characteristics associated with JPH2 mutation. JPH2-hiPSC-CMs displayed key HCM hallmarks (cellular hypertrophy, multi-nucleation, sarcomeric disarray). Moreover, JPH2-hiPSC-CMs exhibit a higher degree of arrhythmia and longer action potential duration associated with slower inactivation of calcium channels. Functional evaluation supported clinical observations, with differences in beating characteristics when compared with isogenic-hiPSC-CMs. Thus, the iPSC-derived, disease-specific cardiomyocytes could serve as a translationally relevant platform to study genetic cardiac diseases.

Case series of catheter-based arrhythmia ablation in pregnant women

Abstract Funding Acknowledgements Type of funding sources: None. Background Antiarrhythmic drugs (AADs) should be used with caution in treating arrhythmias during pregnancy because of side effects, but catheter ablation is a rarely used procedure. Aim To investigate the efficacy and safety of catheter ablation in cardiac arrhythmias during pregnancy. Methods A double-center retrospective case series study was performed. We studied a population of patients undergoing catheter ablation for cardiac arrhythmias during pregnancy between April 2014 and September 2021 in two cardiovascular centers in Hungary. Results 14 procedures [14 electrophysiology studies (EPS), 13 ablations] performed on 13 gravid women (age 30.3±5.2 years, primipara n=6) were studied. The mean gestation period was 24.0 (20.0-27.0) weeks at the time of intervention, and the mean duration of arrhythmia was 44.0±53.0 months. Of the pregnant women 38.5% had comorbidities and 15.4% had structural heart disease. During EPS, 12 patients had inducible arrhythmias. Focal atrial tachycardia was confirmed in 3, AVRT via manifest accessory pathway (AP) in 3 (WPW syndrome) AVRT via counceled AP in 1 case. AVNRT was confirmed in 3, sustained ventricular tachycardia in 2 cases (25-25-8.3-25-16.6%). 11 radiofrequency ablations (RFA) (84.6%) and 2 cryoablations (15.4%) were performed. The electroanatomical mapping system was CARTO in 11 cases (84.6%) and NavX-EnSite in 2 cases (15.4%). Intracardiac echocardiography (ICE) was used in 5 cases (38.5%). Transseptal puncture was performed in 2 cases (15.4%) due to left lateral AP. The average procedure time was 76.0±33.0 min. All the procedures (100.0%) were performed without fluoroscopy. No complications occurred during the procedures. In the long term, arrhythmia-free survival was achieved in all cases (100.0%), but in two patients, we used AADs to achieve freedom of arrhythmia. With AADs, the mean birth weight was lower than that of fetuses of gravidas not taking drugs (2110±1314 vs. 3253±458 g). APGAR was within the normal range in all cases [9.0/10.0 (IQR) (9.0-10.0/9.3-10.0)]. Conclusions Zero-fluoroscopic catheter ablation during pregnancy is an effective and safe treatment method when needed. Catheter ablation for persistent maternal arrhythmias has a more beneficial effect on fetal development than the use of AADs. Indeed, long-term outcome and safety need to be investigated in a larger patient population.

PO-455617-5 ANTI-ARRHYTHMIC EFFECTS OF BIOINSPIRED MODIFIED Y RNA IN RATS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION

Exosomes secreted from cardiosphere-derived cells (CDCs) attenuate ventricular arrhythmias and prolong survival of rats with heart failure and preserved ejection fraction (HFpEF). Y RNA fragments were abundant in exosomes secreted from CDCs, and they mediate the anti-inflammatory and anti-fibrotic effects of CDCs. We tested the hypothesis that bioinspired modified Y RNA decrease ventricular arrhythmias in rats with HFpEF by reversing electrical remodeling. Dahl salt-sensitive (DSS) rats (n=19) were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF. Echocardiogram was performed at 14 weeks of age to confirm the development of diastolic dysfunction (increased E/E’ ratio). Symptomatic rats with diastolic dysfunction were diagnosed with HFpEF. TY1 (Therapeutic Y RNA1, a modified Y RNA in transfection reagent) was injected via the tail vein (twice weekly for 4 weeks) to rats with HFpEF (n=7). Vehicle (phosphate-buffered saline in transfection reagent) and scramble (in transfection reagent) were also injected via the tail vein as placebo (n=8 and 4, respectively). Echocardiogram and programmed electrical stimulation (PES) were performed after 4 weeks of TY1 vs. vehicle or scramble injections. Electrocardiogram was performed to measure QTc intervals as a marker for adverse electrical remodeling. Ventricular arrhythmias were induced in 80% of vehicle-injected and 100% of scramble-injected HFpEF rats by PES, as compared to only 33% of TY1-injected HFpEF rats (p=0.036). The duration of ventricular arrhythmias was significantly lower in TY1-injected HFpEF rats as compared to vehicle-injected and scramble-injected HFpEF rats (4 [IQR 0-5] beats in TY1 vs. 30 [IQR 8-54] beats in vehicle, p=0.034; vs. 21 [16-48] beats in scramble; p=0.031). QTc interval was reduced in TY1-injected HFpEF rats as compared to vehicle or scramble-injected HFpEF rats (QTc interval 238±16 ms in TY1 vs. 271±24 ms in vehicle, p=0.034; vs. 280±7 ms in scramble, p=0.017). Survival was prolonged in TY1-injected HFpEF rats as compared to vehicle or scramble-injected HFpEF rats, although statistically insignificant due to a low number of rats (86% in TY1 vs. 63% in vehicle or 75% in scramble). TY1, a modified Y RNA, reduced ventricular arrhythmias in rats with HFpEF by reversing adverse electrical remodeling of HFpEF (as manifested by a shortened QTc interval). Given these encouraging data, TY1 merits further investigation as a novel therapeutic candidate for ventricular arrhythmias.

PO-02-209 ANTI-ARRHYTHMIC EFFECTS OF BIOINSPIRED MODIFIED Y RNA IN RATS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION

Exosomes secreted from cardiosphere-derived cells (CDCs) attenuate ventricular arrhythmias and prolong survival of rats with heart failure and preserved ejection fraction (HFpEF). Y RNA fragments were abundant in exosomes secreted from CDCs, and they mediate the anti-inflammatory and anti-fibrotic effects of CDCs. We tested the hypothesis that bioinspired modified Y RNA decrease ventricular arrhythmias in rats with HFpEF by reversing electrical remodeling. Dahl salt-sensitive (DSS) rats (n=19) were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF. Echocardiogram was performed at 14 weeks of age to confirm the development of diastolic dysfunction (increased E/E’ ratio). Symptomatic rats with diastolic dysfunction were diagnosed with HFpEF. TY1 (Therapeutic Y RNA1, a modified Y RNA in transfection reagent) was injected via the tail vein (twice weekly for 4 weeks) to rats with HFpEF (n=7). Vehicle (phosphate-buffered saline in transfection reagent) and scramble (in transfection reagent) were also injected via the tail vein as placebo (n=8 and 4, respectively). Echocardiogram and programmed electrical stimulation (PES) were performed after 4 weeks of TY1 vs. vehicle or scramble injections. Electrocardiogram was performed to measure QTc intervals as a marker for adverse electrical remodeling. Ventricular arrhythmias were induced in 80% of vehicle-injected and 100% of scramble-injected HFpEF rats by PES, as compared to only 33% of TY1-injected HFpEF rats (p=0.036). The duration of ventricular arrhythmias was significantly lower in TY1-injected HFpEF rats as compared to vehicle-injected and scramble-injected HFpEF rats (4 [IQR 0-5] beats in TY1 vs. 30 [IQR 8-54] beats in vehicle, p=0.034; vs. 21 [16-48] beats in scramble; p=0.031). QTc interval was reduced in TY1-injected HFpEF rats as compared to vehicle or scramble-injected HFpEF rats (QTc interval 238±16 ms in TY1 vs. 271±24 ms in vehicle, p=0.034; vs. 280±7 ms in scramble, p=0.017). Survival was prolonged in TY1-injected HFpEF rats as compared to vehicle or scramble-injected HFpEF rats, although statistically insignificant due to a low number of rats (86% in TY1 vs. 63% in vehicle or 75% in scramble). TY1, a modified Y RNA, reduced ventricular arrhythmias in rats with HFpEF by reversing adverse electrical remodeling of HFpEF (as manifested by a shortened QTc interval). Given these encouraging data, TY1 merits further investigation as a novel therapeutic candidate for ventricular arrhythmias.

Ability to remotely monitor atrial high-rate episodes using a single-chamber implantable cardioverter-defibrillator with a floating atrial sensing dipole.

To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min…<1 h, 1 h…<24 h, ≥ 24 h). We used the MATRIX registry data to assess the capability of a single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (DX ICD system) to follow this recommendation in patients with standard indication for single-chamber ICD. In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs ≥6 min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min…<1 h, 99.6% (253/254) for episodes 1 h…<24 h, 100% (71/71) for episodes ≥24 h, or 97.5% for all episodes (595/610). The incidence of new-onset AF was 8.2% (119/1451), and in 31.1% of them (37/119), new-onset AF progressed to a higher duration stratum. Nearly 80% of new-onset AF patients had high CHA2DS2-VASc stroke risk, and 70% were not on anticoagulation therapy. Age was the only significant predictor of new-onset AF. A 99.7% detection accuracy for AHRE ≥1 h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression.

A comparative study between angiotensin receptor neprilysin inhibitor (thiorphan/irbesartan) with each of nitrate and carvedilol in a rat model of myocardial ischemic reperfusion injury.

The combined angiotensin receptor neprilysin inhibitor is a promising cardioprotective pharmacological agent. This study investigated the beneficial effects of thiorphan (TH)/irbesartan (IRB), in myocardial ischemia-reperfusion (IR) injury, compared to each of nitroglycerin and carvedilol. Male Wistar rats were divided into five groups (10 rats/group): Sham, untreated I/R, TH/IRB + IR (0.1/10mg/kg), nitroglycerin + IR (0.2mg/kg), and carvedilol + IR (10mg/kg). Mean arterial blood pressure, cardiac functions and arrhythmia incidence, duration and score were assessed. Cardiac levels of creatine kinase-MB (CK-MB), oxidative stress, endothelin-1, ATP, Na+ /K+ ATPase pump activity and mitochondria complexes activities were measured. Histopathological examination, Bcl/Bax immunohistochemistry studies and electron microscopy examination of left ventricle were performed. TH/IRB preserved the cardiac functions and mitochondrial complexes activities, mitigated cardiac damage, reduced oxidative stress and arrhythmia severity, improved the histopathological changes and decreased cardiac apoptosis. TH/IRB showed a comparable effect to each of nitroglycerin and carvedilol in alleviating the IR injury consequences. TH/IRB showed significant preservation of mitochondrial complexes activity I and II compared to nitroglycerin. TH/IRB significantly increased LVdP/dtmax and decreased oxidative stress, cardiac damage and endothelin-1 along with increasing the ATP content, Na+ /K+ ATPase pump activity and mitochondrial complexes activity when compared to carvedilol. TH/IRB showed a cardioprotective effect in reducing IR injury that is comparable to each of nitroglycerin and carvedilol that could be explained in part by its ability to preserve mitochondrial function, increase ATP, decrease oxidative stress as well as endothelin 1.

New Onset Atrial Fibrillation in STEMI Patients: Main Prognostic Factors and Clinical Outcome.

The indications for the treatment of patients with known atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) are clear, while less is available about the management of new-onset AF (NOAF) during ST-segment elevation myocardial infarction (STEMI). The aim of this study is to evaluate mortality and clinical outcome of this high-risk subgroup of patients. We analyzed 1455 consecutive patients undergoing PCI for STEMI. NOAF was detected in 102 subjects, 62.7% males, with a mean age of 74.8 ± 10.6 years. The mean ejection fraction (EF) was 43.5 ± 12.1% and the mean atrial volume was increased (58 ± 20.9 mL). NOAF occurred mainly in the peri-acute phase and had a very variable duration (8.1 ± 12.5 min). During hospitalization, all the patients were treated with enoxaparin, but only 21.6% of them were discharged with long term oral anticoagulation. The majority of patients had a CHA2DS2-VASc score >2 and a HAS-BLED score of 2 or 3. The in-hospital mortality was 14.2%, while the 1-year mortality was 17.2% and long-term mortality 32.1% (median follow-up 1820 days). We identified age as an independent predictor of mortality both at short- and long-term follow-ups, while EF was the only independent predictor for in-hospital mortality and arrhythmia duration for 1-year mortality. At the 1-year follow-up, we recorded three ischemic strokes and no bleeding complications.

Ventricular arrhythmias following balloon-expandable transcatheter pulmonary valve replacement in the native right ventricular outflow tract.

Ventricular arrhythmia incidence in children and adolescents undergoing transcatheter pulmonary valve replacement (TPVR) within the native right ventricular outflow tract (nRVOT) is unknown. We sought to describe the incidence, severity, and duration of ventricular arrhythmias and identify associated risk factors in this population. This was a retrospective cohort study of 78 patients <21 years of age who underwent TPVR within the nRVOT. Patients were excluded for pre-existing ventricular arrhythmia or antiarrhythmic use. Study variables includedsurgical history, valve replacement indication, valve type/size, and ventricular arrhythmia. Univariable logistic regression models were used to evaluate factors associated with ventricular arrhythmias, followed by subset analyses. Nonsustained ventricular arrhythmia occurred in 26/78 patients (33.3%). The median age at the procedure was 10.3 years (interquartle range [IQR]: 6.5, 12.8). Compared with other nRVOT types, surgical repair with transannular patch was protective against ventricular arrhythmia incidence: odds ratio (OR): 0.35 (95% confidence interval [CI], 0.13-0.95). Patient weight, valve type/size, number of prestents, and degree of stent extension into the RVOT were not associated with ventricular arrhythmia occurrence. Beta blocker was started in 16/26 (61.5%) patients with ventricular arrhythmia. One additional patient was lost to follow-up. The median beta blocker duration was 46 days (IQR 42, 102). Beta blocker was discontinued in 10 patients by 8-week follow-up and in the remaining four by 9 months. Though common after balloon-expandable TPVR within the nRVOT, ventricular arrhythmias were benign and transient. Antiarrhythmic medications were successfully discontinued in the majority at 6- to 8-week follow-up, and in all patients by 20 months.